• The Korean Journal of Physiology and Pharmacology
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• 제17권1호
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• pp.99-109
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• 2013

The aim of this study was to determine whether fimasartan, a newly developed $AT_1$ receptor blocker, can affect the CA release in the isolated perfused model of the adrenal medulla of spontaneously hypertensive rats (SHRs). Fimasartan (5~50 ${\mu}M$) perfused into an adrenal vein for 90 min produced dose- and time-dependently inhibited the CA secretory responses evoked by ACh (5.32 mM), high $K^+$ (56 mM, a direct membrane depolarizer), DMPP (100 ${\mu}M$) and McN-A-343 (100 ${\mu}M$). Fimasartan failed to affect basal CA output. Furthermore, in adrenal glands loaded with fimasartan (15 ${\mu}M$), the CA secretory responses evoked by Bay-K-8644 (10 ${\mu}M$, an activator of L-type $Ca^{2+}$ channels), cyclopiazonic acid (10 ${\mu}M$, an inhibitor of cytoplasmic $Ca^{2+}$-ATPase), and veratridine (100 ${\mu}M$, an activator of $Na^+$ channels) as well as by angiotensin II (Ang II, 100 nM), were markedly inhibited. In simultaneous presence of fimasartan (15 ${\mu}M$) and L-NAME (30 ${\mu}M$, an inhibitor of NO synthase), the CA secretory responses evoked by ACh, high $K^+$, DMPP, Ang II, Bay-K-8644, and veratridine was not affected in comparison of data obtained from treatment with fimasartan (15 ${\mu}M$) alone. Also there was no difference in NO release between before and after treatment with fimasartan (15 ${\mu}M$). Collectively, these experimental results suggest that fimasartan inhibits the CA secretion evoked by Ang II, and cholinergic stimulation (both nicotininc and muscarinic receptors) as well as by membrane depolarization from the rat adrenal medulla. It seems that this inhibitory effect of fimasartan may be mediated by blocking the influx of both $Na^+$ and $Ca^{2+}$ through their ion channels into the rat adrenomedullary chromaffin cells as well as by inhibiting the $Ca^{2+}$ release from the cytoplasmic calcium store, which is relevant to $AT_1$ receptor blockade without NO release.

• The Korean Journal of Physiology and Pharmacology
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• 제14권4호
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• pp.241-248
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• 2010

The present sutdy aimed to determine whether olmesartan, an angiotensin II (Ang II) type 1 ($AT_1$) receptor blocker, can influence the CA release from the isolated perfused model of the rat adrenal medulla. Olmesartan ($5{\sim}50{\mu}M$) perfused into an adrenal vein for 90 min produced dose- and time-dependent inhibition of the CA secretory responses evoked by ACh (5.32 mM), high $K^+$ (56 mM, a direct membrane-depolarizer), DMPP (100 ${\mu}M$) and McN-A-343 (100 ${\mu}M$). Olmesartan did not affect basal CA secretion. Also, in adrenal glands loaded with olmesartan (15 ${\mu}M$), the CA secretory responses evoked by Bay-K-8644 (10 ${\mu}M$, an activator of voltage-dependent L-type $Ca^{2+}$ channels), cyclopiazonic acid (10 ${\mu}M$, an inhibitor of cytoplasmic $Ca^{2+}$-ATPase), veratridine (100 ${\mu}M$, an activator of voltage-dependent $Na^+$ channels), and Ang II (100 nM) were markedly inhibited. However, at high concentrations ($150{\sim}300{\mu}M$), olmesartan rather enhanced the ACh-evoked CA secretion. Taken together, these results show that olmesartan at low concentrations inhibits the CA secretion evoked by cholinergic stimulation (both nicotininc and muscarinic receptors) as well as by direct membrane depolarization from the rat adrenal medulla, but at high concentrations it rather potentiates the ACh-evoked CA secretion. It seems that olmesartan has a dual action, acting as both agonist and antagonist at nicotinic receptors of the isolated perfused rat adrenal medulla, which might be dependent on the concentration. It is also thought that this inhibitory effect of olmesartan may be mediated by blocking the influx of both $Na^+$ and $Ca^{2+}$ into the rat adrenomedullary chromaffin cells as well as by inhibiting the $Ca^{2+}$ release from the cytoplasmic calcium store, which is thought to be relevant to the $AT_1$ receptor blockade, in addition to its enhancement on the CA secreton.

• 생약학회지
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• 제50권4호
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• pp.253-259
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• 2019

Chaenomeles speciose Nakai (CSP) or Chaenomeles sinensis Koehne (CSS) (Rosaceae) has been used, traditionally, to treat muscle problems and gastric dampness in eastern Asia countries. Therefore, many studies have focused on investigating its active compounds and effects on muscle pain, arthritis and gastro-intestinal diseases. Recently, several studies reported that CSS extract degrade amyloid plaques and enhance synaptic acetylcholine level in vivo and in vitro. Although these two Chaenomeles species are used without differences, CSP is reported to contains more phenolic compounds which are known to enhance memory. Therefore, in this study, we investigated the memory ameliorating effects of CSP by employing the passive avoidance test, Y-maze task and novel object recognition test. CSP (30 or 100 mg/kg) ameliorated the declined memory induced by scopolamine injection and enhanced the brain-derived neurotrophic factor (BDNF) levels along with post synaptic density protein 95 (PSD 95) levels at the hippocampus of the scopolamine-injected mouse brain. These results suggested that CSP alleviates the cognition declines caused by cholinergic blockade via enhancing BDNF levels and PSD 95, and that it would enhance memory formation and be useful for treating memory declines.

• Journal of Ginseng Research
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• 제35권2호
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• pp.176-190
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• 2011

There seems to be some controversy about the effect of total ginseng saponin (TGS) on the secretion of catecholamines (CA) from the adrenal gland. Therefore, the present study aimed to determine whether TGS can affect the CA release in the perfused model of the adrenal medulla isolated from spontaneously hypertensive rats (SHRs). TGS (15-150 ${\mu}g/mL$), perfused into an adrenal vein for 90 min, inhibited the CA secretory responses evoked by acetylcholine (ACh, 5.32 mM) and high $K^+$ (56 mM, a direct membrane depolarizer) in a dose- and time-dependent fashion. TGS (50 ${\mu}g/mL$) also time-dependently inhibited the CA secretion evoked by 1.1-dimethyl-4 -phenyl piperazinium iodide (DMPP; 100 ${\mu}M$, a selective neuronal nicotinic receptor agonist) and McN-A-343 (100 ${\mu}M$, a selective muscarinic M1 receptor agonist). TGS itself did not affect basal CA secretion (data not shown). Also, in the presence of TGS (50 ${\mu}g/mL$), the secretory responses of CA evoked by veratridine (a selective $Na^+$ channel activator (50 ${\mu}M$), Bay-K-8644 (an L-type dihydropyridine $Ca^{2+}$ channel activator, 10 ${\mu}M$), and cyclopiazonic acid (a cytoplasmic $Ca^{2+}$-ATPase inhibitor, 10 ${\mu}M$) were significantly reduced, respectively. Interestingly, in the simultaneous presence of TGS (50 ${\mu}g/mL$) and N${\omega}$-nitro-L-arginine methyl ester hydrochloride [an inhibitor of nitric oxide (NO) synthase, 30 ${\mu}M$], the inhibitory responses of TGS on the CA secretion evoked by ACh, high $K^+$, DMPP, McN-A-343, Bay-K-8644, cyclopiazonic acid, and veratridine were considerably recovered to the extent of the corresponding control secretion compared with the inhibitory effect of TGS-treatment alone. Practically, the level of NO released from adrenal medulla after the treatment of TGS (150 ${\mu}g/mL$) was greatly elevated compared to the corresponding basal released level. Taken together, these results demonstrate that TGS inhibits the CA secretory responses evoked by stimulation of cholinergic (both muscarinic and nicotinic) receptors as well as by direct membrane-depolarization from the isolated perfused adrenal medulla of the SHRs. It seems that this inhibitory effect of TGS is mediated by inhibiting both the influx of $Ca^{2+}$ and Na+ into the adrenomedullary chromaffin cells and also by suppressing the release of $Ca^{2+}$ from the cytoplasmic calcium store, at least partly through the increased NO production due to the activation of nitric oxide synthase, which is relevant to neuronal nicotinic receptor blockade, without the enhancement effect on the CA release. Based on these effects, it is also thought that there are some species differences in the adrenomedullary CA secretion between the rabbit and SHR.